VCV002665054.1 - ClinVar

GRCh38/hg38 1q21.1-21.2(chr1:146872717-148353641)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh38/hg38 1q21.1-21.2(chr1:146872717-148353641)

Variation ID: 2665054 Accession: VCV002665054.1

Type and length

copy number loss, -

Location

Cytogenetic: 1q21.1-21.2 1: 146185876-148483033 (GRCh38) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 17, 2023	Dec 17, 2023	Aug 10, 2023

HGVS

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GJA5		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	-	-
GJA8		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	-	-
CHD1L		No evidence available	No evidence available	GRCh38 GRCh37	-	-
ACP6		-	-	GRCh38 GRCh37	-	-
BCL9		-	-	GRCh38 GRCh37	-	-
CH17-408M7.1	-	-	-	GRCh38	-	-
FMO5		-	-	GRCh38 GRCh37	-	-
GPR89B		-	-	GRCh38 GRCh37	-	-
LINC00624	-	-	-	GRCh38	-	-
LINC01138	-	-	-	GRCh38	-	-

There are 51 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
1q21.1 microdeletion syndrome (BP3-BP4, distal)	Pathogenic (1)	criteria provided, single submitter	Aug 10, 2023	RCV003448604.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 10, 2023)	criteria provided, single submitter (NYGC Assertion Criteria 2020) Method: clinical testing	1q21.1 microdeletion syndrome (BP3-BP4, distal) Affected status: yes Allele origin: de novo	New York Genome Center Accession: SCV004176129.1 First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023	Comment: This ~1.48 Mb deletion completely overlaps with the recurrent 1q21.1 microdeletion syndrome occurring between BP3-BP4 breakpoints, which has been curated by ClinGen to have a … (more) This ~1.48 Mb deletion completely overlaps with the recurrent 1q21.1 microdeletion syndrome occurring between BP3-BP4 breakpoints, which has been curated by ClinGen to have a "sufficient evidence for haploinsufficiency" [https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37421]. Recurrent 1q21.1 deletions similar to the one identified here have previously been reported in multiple individuals in the literature with mild neurodevelopmental delay, dysmorphic facial features, eye abnormalities including cataract, structural and valvular heart defects, skeletal abnormalities including scoliosis, joint laxity, brachydactyly, broad or duplicated/bifid great toes, overlapping or syndactyly of the toes, and polydactyly of the hands or feet, and genitourinary abnormalities including vesicoureteral reflux, hydronephrosis, inguinal hernia, and cryptorchidism. Postnatal short stature, failure to thrive, and growth retardation have also been reported. Some of these phenotypes may manifest prenatally [doi.org/10.1155/2022/5487452]. Phenotypic variability and incomplete penetrance have been observed [PMID: 21348049]. Based on available evidence this de novo deletion at 1q21.1q21.2 is classified as Pathogenic. (less) Number of individuals with the variant: 1 Clinical Features: Fetal growth restriction (present) , Failure to thrive (present) , Short stature (present) , Upper lip pit (present) , Postaxial polysyndactyly of foot (present) Secondary finding: no

Comment:

This ~1.48 Mb deletion completely overlaps with the recurrent 1q21.1 microdeletion syndrome occurring between BP3-BP4 breakpoints, which has been curated by ClinGen to have a "sufficient evidence for haploinsufficiency" [https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37421]. Recurrent 1q21.1 deletions similar to the one identified here have previously been reported in multiple individuals in the literature with mild neurodevelopmental delay, dysmorphic facial features, eye abnormalities including cataract, structural and valvular heart defects, skeletal abnormalities including scoliosis, joint laxity, brachydactyly, broad or duplicated/bifid great toes, overlapping or syndactyly of the toes, and polydactyly of the hands or feet, and genitourinary abnormalities including vesicoureteral reflux, hydronephrosis, inguinal hernia, and cryptorchidism. Postnatal short stature, failure to thrive, and growth retardation have also been reported. Some of these phenotypes may manifest prenatally [doi.org/10.1155/2022/5487452]. Phenotypic variability and incomplete penetrance have been observed [PMID: 21348049]. Based on available evidence this de novo deletion at 1q21.1q21.2 is classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Dec 17, 2023

ClinVar Genomic variation as it relates to human health

GRCh38/hg38 1q21.1-21.2(chr1:146872717-148353641)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...